This is a Competing Continuation application for a Training Grant (TG) at the Johns Hopkins Univ. School of Medicine for the Training of Post-doctoral Fellows (MD, MD/PhD or PhD) for long-term investigative careers in basic and clinical investigation in Gastroenterology. This program has strong basic science investigators in the GI Division; a formal 4 year program for training clinical investigators done in collaboration with the Hopkins School of Hygiene and Public Health which usually results in a Ph.D in clinical research; close interactions with Basic Scientists at Hopkins; a closely knit group of scientists at Hopkins interested in epithelial cell and molecular biology and transcriptional regulation; and two NIDDK Center Grants at Hopkins, one which advances research in epithelial cell and molecular biology (Hopkins Digestive Diseases Basic Research Development Core Center), and the other which advances translational research (NASH Clinical Research Center). The TG Faculty (21) have primary appointments in the GI Division (14); Departments of Cell Biology (1); Physiology (2); Biological Chemistry (1); other Dept. of Medicine (1); Pathology (1); Surgery (1). Some of the areas of expertise fellows will be trained in include: Basic Research Areas: (1) Regulation of intestinal and hepatic electrolyte transport by epithelial cells. (2) Identification and characterization of epithelial Na+ transport proteins. (3) Trafficking of GI and liver proteins, including NHE3 and Menke's and Wilson's proteins. (4) Transcriptional regulation involved in epithelial cell differentiation and in hepatocyte regeneration post liver resection and in hormonal regulation of alcohol metabolizing enzymes. (5) Identification of genetic contributions to Crohn's disease and genes and proteins which are altered in IBD. (6) Regulation of hepatic collagen formation. (7) Models of hepatic steatosis. (8) GI stem cells. Clinical Research Areas: (1) Family studies of Crohn's disease to distinguish different types of disease; (2) Epigenetic studies of GI cancers. (3) Health outcomes studies of use of endoscopic ultrasound in biliary tract diseases. (4) NASH - causes and treatment. A total of 5 Training Grant slots are requested per year to be used for 3 or 4 MD or MD/PhD and 1 or 2 PhD Fellows. The program is for 2-3 years in the laboratory or 3 years of clinical research leading to a Ph.D. in clinical research, in addition to a clinical year not supported by the TG. All Fellows are assigned a Fellowship Committee which helps monitor their progress in attaining a long term investigative career, critiques their research, and helps decide on need for formal courses to supplement their research. Fellows who are thought to be successful in being prepared for investigative careers are helped to obtain bridging support and brought on as junior faculty to allow adequate time for training.